title: What have we learned from clinical trials in primary Sjögren's syndrome about pathogenesis?
abstract: In vitro and in vivo experimental data have pointed to new immunopathogenic mechanisms in primary Sjögren's syndrome (pSS). The availability of targeted treatment modalities has opened new ways to selectively target these mechanistic pathways in vivo. This has taught us that the role of proinflammatory cytokines, in particular TNFα, is not crucial in the immunopathogenesis of pSS. B cells appear to play a major role, as depletion of B cells leads to restoration of salivary flow and is efficacious for treatment of extraglandular manifestations and mucosa-associated lymphoid tissue lymphoma. B cells also orchestrate T-cell infiltration and ductal epithelial dearrangement in the salivary glands. Gene profiling of salivary gland tissue in relation to B-cell depletion confirms that the axis of IFNα, B-cell activating factor, B-cell activation, proliferation and survival constitutes a major pathogenic route in pSS.
authors.affiliation: Department of Rheumatology and Clinical Immunology, AA21, University Medical Center Groningen, University of Groningen, P.O. Box 30001, 9700 RB Groningen, The Netherlands. c.g.m.kallenberg@int.umcg.nl
authors.forename: Cees G M
authors.initials: CG
authors.lastname: Kallenberg
authors.forename: Arjan
authors.initials: A
authors.lastname: Vissink
authors.forename: Frans G M
authors.initials: FG
authors.lastname: Kroese
authors.forename: Wayel H
authors.initials: WH
authors.lastname: Abdulahad
authors.forename: Hendrika
authors.initials: H
authors.lastname: Bootsma
mesh_terms: D018501:Antirheumatic Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D006801:Humans; D012859:Sjogren's Syndrome / Q000188:drug therapy* / Q000276:immunology* / Q000503:physiopathology
chemical_list: D018501:Antirheumatic Agents